Justicidin A decreases the level of cytosolic Ku70 leading to apoptosis in human colorectal cancer cells

Jenq Chang Lee, Chao-Hung Lee, Chun Li Su, Chung Wei Huang, Chun Nan Lin, Shen Jeu Won

Research output: Contribution to journalArticle

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Abstract

The natural product justicidin A, an arylnaphthalide lignan isolated from Justicia procumbens, significantly inhibited the growth of human colorectal cancer cells HT-29 and HCT 116 at day 6 post-treatment. Further study revealed that justicidin A-treated HT-29 and HCT 116 colorectal cancer cells died of apoptosis. Justicidin A treatment caused DNA fragmentation and an increase in phosphatidylserine exposure of the cells. The number of cells in the sub-G1 phase was also increased upon justicidin A treatment. Caspase-9 but not caspase-8 was activated, suggesting that justicidin A treatment damaged mitochondria. The mitochondrial membrane potential was altered and cytochrome c and Smac were released from mitochondria to the cytoplasm upon justicidin A treatment. The level of Ku70 in the cytoplasm was decreased, but that of Bax in mitochondria was increased by justicidin A. Since Ku70 normally binds and sequesters Bax, these results suggest that justicidin A decreases the level of Ku70 leading to translocation of Bax from the cytosol to mitochondria to induce apoptosis. Oral administration of justicidin A was shown to suppress the growth of HT-29 cells transplanted into NOD-SCID mice, suggesting chemotherapeutic potential of justicidin A on colorectal cancer cells.

Original languageEnglish
Pages (from-to)1716-1730
Number of pages15
JournalCarcinogenesis
Volume26
Issue number10
DOIs
StatePublished - Oct 2005

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Colorectal Neoplasms
Apoptosis
Mitochondria
HT29 Cells
Justicia
Cytoplasm
justicidin A
Therapeutics
Lignans
Inbred NOD Mouse
SCID Mice
Caspase 9
Caspase 8
Mitochondrial Membrane Potential
Phosphatidylserines
G1 Phase
DNA Fragmentation
Growth
Cytochromes c
Biological Products

ASJC Scopus subject areas

  • Cancer Research

Cite this

Justicidin A decreases the level of cytosolic Ku70 leading to apoptosis in human colorectal cancer cells. / Lee, Jenq Chang; Lee, Chao-Hung; Su, Chun Li; Huang, Chung Wei; Lin, Chun Nan; Won, Shen Jeu.

In: Carcinogenesis, Vol. 26, No. 10, 10.2005, p. 1716-1730.

Research output: Contribution to journalArticle

Lee, Jenq Chang ; Lee, Chao-Hung ; Su, Chun Li ; Huang, Chung Wei ; Lin, Chun Nan ; Won, Shen Jeu. / Justicidin A decreases the level of cytosolic Ku70 leading to apoptosis in human colorectal cancer cells. In: Carcinogenesis. 2005 ; Vol. 26, No. 10. pp. 1716-1730.
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